Decreased pulmonary levels of the anti-inflammatory Clara cell 16 kDa protein after induction of airway inflammation in asthmatics

The Clara cell 16 kDa protein (CC16) maps to an atopy-associated region of chromosome 11 and has been ascribed an anti-inflammatory function. Using reverse-phase HPLC and Western blot analysis, we have evaluated the polypeptide pattern in bronchoalveolar lavage (BAL) fluid retrieved from asthmatics, before and after induction of airway inflammation by low-dose allergen inhalation challenge. A prominent decrease of CC16 was seen after induction of inflammation, and a further CC16 decrease was observed in lavage fluid where surfactant had been removed. Reduced levels of pulmonary CC16 may cause loss of anti-inflammatory activity in the airways and contribute to the development of airway inflammation in asthma. Received 22 March 2000; received after revision 4 May 2000; accepted 4 May 2000     

Adjusting for information content when comparing forecast performance

Cross‐institutional forecast evaluations may be severely distorted by the fact that forecasts are made at different points in time and therefore with different amounts of information. This paper proposes a method to account for these differences when analyzing an unbalanced panel of forecasts. The method computes the timing effect and the forecaster's ability simultaneously. Monte Carlo simulation demonstrates that evaluations that do not adjust for the differences in information content may be misleading. In addition, the method is applied to a real‐world dataset of 10 Swedish forecasters for the period 1999–2015. The results show that the ranking of the forecasters is affected by the proposed adjustment.     

Aquatic insects in the forest canopy: a new genus of moth flies (Diptera: Psychodidae) developing in slime on aerial roots

Many hemiepiphytic plants secrete a thick layer of mucilage to limit desiccation and protect against fungal pathogens. With its stable moisture and protected location, this mucilage constitutes a potentially attractive microhabitat for small animals; however, until now, no animal species have been recorded from it. Larvae of a psychodid fly were collected from the mucilage of a hemiepiphytic Araceae in Braulio Carillo National Park, Costa Rica. Rearing of the larvae yielded specimens of pupae and one adult male described here as Mucomyia emersa Kvifte and Curler gen. nov. sp. nov. An additional species from Costa Rica, Mucomyia browni Kvifte sp. nov., is described based on adult males from the Zurquí de Moravia forest reserve. Mucomyia belongs to tribe Psychodini, which comprises both habitat generalists and specialists. The new species are morphologically similar to those in Philosepedon s. str. and Eurygarka, both of which are known to develop in snail carrion. It is premature to speculate about whether or not species in the new genus are restricted to hemiepiphyte mucilage.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:37CD136B-53D8-4D3E-A34A-3BE4859045E5     

Rate of de novo mutations and the importance of father's age to disease risk

Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. We show that in our samples, with an average father's age of 29.7, the average de novo mutation rate is 1.20?×?10(-8) per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5?years. After accounting for random Poisson variation, father's age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism.     

Novel role of PKR in inflammasome activation and HMGB1 release

The inflammasome regulates the release of caspase activation-dependent cytokines, including interleukin (IL)-1β, IL-18 and high-mobility group box 1 (HMGB1). By studying HMGB1 release mechanisms, here we identify a role for double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminium, rotenone, live Escherichia coli, anthrax lethal toxin, DNA transfection and Salmonella typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1β, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with several inflammasome components, including NOD-like receptor (NLR) family pyrin domain-containing 3 (NLRP3), NLRP1, NLR family CARD domain-containing protein 4 (NLRC4), absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell-free system with recombinant NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC, also known as PYCARD) and pro-caspase-1 reconstitutes inflammasome activity. These results show a crucial role for PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation.     

Constructive Scaffolding or a Procrustean Bed? Exploring the Influence of a Facilitated,Structured Group Process in a Climate Action Group

In this paper we present a case of a structured, facilitated group process with a climate action group engaged in a local Transition initiative. We explore how the interacting contexts between action researchers and the group acted as a constraint for the trajectory of the group process, by looking at the mismatches between the group’s and the researchers’ purposes and differences in expectations about methods of engagement. A methodological framework was used for evaluating the outcomes. The primary aim of this article was to investigate and point out dynamics that may be a hindrance to the effectiveness of a facilitated local climate initiative, with the view to inform facilitation practices and improve future action research processes.